Iron and Palladium Catalyzed C-H Functionalization [Elektronische Ressource] / Wei Han. Betreuer: Herbert Mayr

Dissertation zur Erlangung des Doktorgrades
der Fakultät für Chemie und Pharmazie
der Ludwig-Maximilians-Universität München









Iron and Palladium Catalyzed C-H Functionalization









WEI HAN


aus


Hubei, China






2011






Erklärung



Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29. Januar
1998 (in der Fassung der sechsten Änderungssatzung vom 16. August 2010) von Herrn Prof. Dr.
Herbert Mayr betreut.






Ehrenwörtliche Versicherung



Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe erarbeitet.




München, …12.05.2011…






……………………………
WEI HAN








Dissertation eingereicht am 12.05.2011

1. Gutachter: Prof. Dr. Herbert Mayr

2. Gutachter: Prof. Dr. Hendrik Zipse

Mündliche Prüfung am 22.06.2011

























...dedicated to my parents




























Acknowledgements

First of all, I would like to sincerely thank Professor Dr. Herbert Mayr for offering me the
opportunity to work in his group, especially for allowing me independently free exploration
and giving me generous support.

I greatly appreciate Dr. Armin Ofial, who is patient, considerate and conscientious, for helpful
discussions, critical comments and valuable suggestions. I have learned a lot from him and I
am grateful for his guidance in using experimental devices and showing me useful materials
for research.

I would like to express my gratitude to Prof. Dr. Hendrik Zipse for reviewing and
commenting my thesis. And I also thank all other professors as my referees.

I must acknowledge the China Scholarship Council for financial support.

I would like to thank Frau Dubler and Dr. Stephenson for the measurement of NMR spectra,
Dr. P. Mayer for determing crystal structures, Dr. Konrad Koszinowski for the measurement
of MS and Dr.Marianne Rotter for the XRD measurements.

Special thanks to Dr. Lei Shi, Dr. Sami Lakhdar, Markus Horn, Alexander Wagner, Elija
Wiedemann, Dr. Roland Appel, Dr. Yue Tan, Xi Chen, Xingwei Guo, Dr. Saloua Chelli, Dr.
Guillaume Berionni, Hans Laub and Konstantin Troshin for good suggestions, useful
discussions or nice talk. I have to say “thank you “ to Markus Horn again for his unique
patience to translate German to English for me over the years.

I would also like to thank Prof. H. Mayr Group past and present members J. Fleckenstein,
Christoph Nolte, B. Maji, Dr. H. Asahara, A. Antipova, J. Ammer, Dr. O. Kaumanns, Dr. H.
Schaller, Dr. D. Richter, F. Corral, I. Zenz, D. Allgäuer, Dr. M. Breugst, Dr. T. Kanzian, Dr.
N. Streidl and T. Nigst. It has been a pleasure to work alongside of each of you.

I would like to sincerely thank Nathalie Hampel for continuous help. Her kindness and
patience are impressive. I really appreciate that. And I would also like to thank Frau H.
Lipfert for patient and thoughtful help. Additionally, I thank Brigitte Janker for ordering
chemicals and glasswares.


I especially thank Consulate General of China in München and the international office of
LMU for their kind help since my first arrival to Munich.


I would like to express my deep and cordial gratitude to my chinese friends and german
friends for generous help and support.


Finally, I am fully indebted to my parents, my brothers and my whole family, who always
show their patience, encouragement and support over the years.





Parts of this Ph.D. thesis have been published:



Iron Catalyzed Oxidative Cyanation of Tertiary Amines
Wei Han, Armin R. Ofial, Chem. Commun. 2009, 5024–5026.

Iron-Catalyzed Dehydrogenative Phosphonation of N,N-Dimethylanilines
Wei Han, Armin R. Ofial, Chem. Commun. 2009, 6023–6025.

Iron-Catalyzed Oxidative Mono- and Bis-phosphonation of N,N-Dialkylanilines
Wei Han, Peter Mayer, Armin R. Ofial, Adv. Synth. Catal. 2010, 352, 1667-1676.

trans-1-Phenylpyrrolidine-2,5-dicarbonitrile
Wei Han, Armin R. Ofial, Peter Mayer, Acta Crystallogr., Sect. E: Struct. Rep. Online 2010,
66, o397.

Palladium-Catalyzed Dehydrogenative Cross Couplings of Benzazoles with Azoles
Wei Han, Peter Mayer, Armin R. Ofial, Angew. Chem. Int. Ed. 2010, 50, 2178-2182.

Palladium-Catalyzed Direct Arylations of Azoles with Aryl Silicon and Tin Reagents
Wei Han, Peter Mayer, Armin R. Ofial, Chem. Eur. J. 2011, 17, 6904-6908.





Conference Attended:

Catalytic and Highly Selective Double C-H Bonds Cross-Coupling of Azoles
rdWei Han, Armin R. Ofial, 3 EuCheMs Chemistry Congress, Nürnberg, Germany, 2010,
(Poster Presentation).




Table of Contents



Chapter 0 Summary


1 0.1 General

1 0.2 Fe Catalyzed C-H Bond Activation
1 0.2.1 Iron Catalyzed Oxidative Cyanation of Tertiary Amines
0.2.2 Iron-Catalyzed Dehydrogenative Phosphonation of N,N-
4 Dialkylanilines
0.3 Palladium-Catalyzed Direct Arylations of Azoles with
Aryl Silicon and Tin Reagents 5
0.4 Palladium-Catalyzed Dehydrogenative Cross Couplings
of Azoles 7
0.5 Palladium-Catalyzed Direct Trifluoromethylation of
2Azoles via sp C-H Activation 8


Chapter 1 Introduction



1.1 General Overview 10
11 1.2 Fe-Catalyzed Organic Reactions
11 1.2.1 Overview
3 11 1.2.2 Functionalization of sp C–H Bonds Adjacent to Nitrogen
2 22 1.3 Pd-Catalyzed Direct Arylation of sp C-H Bonds
22 1.3.1 Overview
2 1.3.2 Pd-Catalyzed Direct Arylation of sp C-H with Organometallic

26 Reagents
33 1.3.3 Pd-Catalyzed Direct C-H/C-H Cross-Coupling of Arenes
45 1.4 Transition-Metal-Catalyzed Arene Trifluoromethylation
53 1.5 Objectives
55 1.6 References


Chapter 2 Iron Catalyzed Oxidative Cyanation of
Tertiary Amines

62 2.1 Introduction
65 2.2 Results and Discussion
65 2.2.1 Optimizing the Catalytic System
67 2.2.2 Scope and Limitations
72 2.2.3 Oxygen as Oxidant
76 2.3 Conclusion
77 2.4 References
79 2.5 Experimental Section
79 2.5.1 General
79 2.5.2 Materials
2.5.3 Iron-Catalyzed Cyanation of Tertiary Amines with tert-Butyl

hydroperoxide as Oxidant 80
2.5.4 Iron-Catalyzed Cyanation of Tertiary Amines with Oxygen

as Oxidant 93
2.5.5 X-Ray Crystal Structure Analysis of 1-Phenylpyrrolidine-2,5-

dicarbonitrile 98



Chapter 3 Iron-Catalyzed Dehydrogenative
Phosphonation of N,N-Dialkylanilines

100 3.1 Introduction
102 3.2 Results and Discussion
102 3.2.1 α-Phosphonation
110 3.2.2 α, α’-Bisphosphonations
111 3.2.3 Mechanism
113 3.3 Conclusions
114 3.4 References
119 3.5 Experimental Section
119 3.5.1 General
119 3.5.2 Materials
3.5.3 Typical Procedure for the Iron Catalyzed Phosphonation of
120 Tertiary Amines
120 3.5.4 Phosphonated Tertiary Amines
144 3.5.5 Reactions of the N,O-acetal 27a with 2a
144 3.5.6 In Situ Experiment for Slow Formation of CH OD 3
146 3.5.7 X-Ray Crystal Structure Analysis of 3s


Chapter 4 Palladium-Catalyzed Direct Arylations of
Azoles with Aryl Silicon and Tin Reagents

148 4.1 Introduction
153 4.2 Results and Discussion
153 4.2.1 Optimizing the Catalytic System

156 4.2.2 Scope and Limitations
160 4.2.3 Mechanism
163 4.3 Conclusion
163 4.4 References
167 4.5 Experimental Section
167 4.5.1 General
167 4.5.2 Materials
4.5.3 Palladium-Catalyzed Direct Coupling of Azoles with Trialkoxy-
167 (aryl)silanes
4.5.4 Palladium-Catalyzed Direct Coupling of Azoles with Allyl-
175 triphenylstannane
178 4.5.5 X-Ray Crystal Structure Analysis of 5


Chapter 5 Palladium-Catalyzed Dehydrogenative Cross
Couplings of Azoles

180 5.1 Introduction
183 5.2 Results and Discussion
183 5.2.1 Scope and Limitations
192 5.2.2 Mechanism
194 5.3 Conclusion
195 5.4 References